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Evidence from in vitro and in vivo studies indicates that these fragments are not merely degradation products but possess distinct biological activities, actively modulating immune signaling and contributing to both acute and chronic inflammatory processes. Here, we provide an overview of proteases and their inhibitors, with a particular focus on peptide fragments generated through proteolytic cleavage. Special emphasis is placed on fragments derived from \u03b11\u2010antitrypsin (AAT), an acute\u2010phase glycoprotein and major inhibitor of neutrophil elastase and other serine proteases. AAT\u2010derived peptides of varying lengths, generated by both target and nontarget proteases, including metalloproteases, have been detected in human biological fluids and tissues. Beyond reflecting proteolytic activity, these peptides provide clinically relevant information on disease\u2010associated inflammation and tissue remodeling. Accordingly, they are emerging as promising diagnostic, monitoring, and predictive biomarkers. Here, we summarize current knowledge on cleaved AAT fragments, their biological functions, and their potential clinical applications.<\/jats:p>","DOI":"10.1155\/mi\/6516930","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T07:24:58Z","timestamp":1788161098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein Fragments: From Biomarkers to Therapeutic Targets\u2014A Focus on \u03b11\u2010Antitrypsin\u2010Derived Peptides"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9266-1293","authenticated-orcid":false,"given":"Friedemann","family":"B\u00f6rner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Iwanicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Held","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Chorostowska-Wynimko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-0324","authenticated-orcid":false,"given":"Aleksandra","family":"Jezela- Stanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-5258","authenticated-orcid":false,"given":"Sabina","family":"Janciauskiene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00120"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35795-8"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.261"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aller.2016.10.011"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00160.x"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00107"},{"key":"e_1_2_11_7_2","doi-asserted-by":"crossref","first-page":"12824","DOI":"10.1074\/jbc.M513331200","article-title":"Substrate Profiling of Cysteine Proteases Using a Combinatorial Peptide Library Identifies Functionally Unique Specificities","volume":"281","author":"Choe Y.","year":"2006","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411930040020401"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249739"},{"key":"e_1_2_11_10_2","first-page":"79","volume-title":"Matrix Metalloproteinase Protocols","author":"Overall C. 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